Presentation is loading. Please wait.

Presentation is loading. Please wait.

Stefano Savonitto, Claudio Cavallini Dipartimento di Cardiologia e Cardiochirurgia Angelo De Gasperis Ospedale Niguarda Ca Granda, Milano Divisione di.

Similar presentations


Presentation on theme: "Stefano Savonitto, Claudio Cavallini Dipartimento di Cardiologia e Cardiochirurgia Angelo De Gasperis Ospedale Niguarda Ca Granda, Milano Divisione di."— Presentation transcript:

1

2 Stefano Savonitto, Claudio Cavallini Dipartimento di Cardiologia e Cardiochirurgia Angelo De Gasperis Ospedale Niguarda Ca Granda, Milano Divisione di Cardiologia, Pr. Osp. Ca Foncello, Treviso Come considerare la positività dei marker di necrosi dopo procedure interventistiche coronariche

3 Elevazione degli indicatori di danno miocardico dopo rivascolarizzazione percutanea CK-MB 10-25% Troponina T o I 20-40%

4 Typical rise and gradual fall (troponin) or more rapid rise and fall (CK-MB)of biochemical markers of myocardial necrosis (above 99 th percentile) with at least one of the following. (a) ischemic symptoms (b) development of Q-wave at ecg (c) ECG changes indicative of ischemia (d) coronary artery intervention ECS/ACC Consensus document for redefinition of Myocardial infarction Eur Heart J.2000; 21.1502-13.

5 ACC/AHA percutaneous coronary guidelines …The writing committee recommends that a CK-MB determination be performed on all patients who have signes or sympthoms suggestive of MI following the procedure or in patients in whom there is angiographic evidence of abrupt vessel closure, important side branch occlusion, or persistent slow flow. (in these circumstances)…., a CK-MB > 3 times the upper limit of normal would constitute a clinically significant MI J Am Coll Cardiol 2001; 37:1-66

6 Post PCI MI- EPIC, EPILOG, Capture, IMPACT II, PURSUIT Spontaneous MI - GUSTO IV ACS, PURSUIT Minor Myocardial Damage and prognosis: Are spontaneous and PCI-related events differents? CK-MB/ULN SPONTANEOUS POST- PCI 6-months mortality Akkerhuis, JACC 2001;37:355a 0-1 >1-3 >3-5 >5-10 >10 4.1 8.62.2 9.02.3 14.33.9 15.64.3 1.3 2.01.5 2.31.8 4.33.4 7.46.1 R.R. R.R. p 0.33 0.54 0.71 0.23

7 Problemi nella interpretazione degli studi ck-release/prognosi studi retrospettivi o analisi post-hoc selezione dei pazienti (trial clinici) inadeguata durata follow-up assenza di analisi multivariata insufficiente dimensione del campione

8 CK-RELEASE dopo PCI Substrato fisiopatologico Correlati clinici, angiografici e procedurali Impatto prognostico Esiste un rapporto di causa/effetto?

9 Post-PCI CK-MB elevation represents myonecrosis Ricciardi Circulation 2001; 103:2780-2783 14 patients with no previous MI and TIMI 3 flow post procedure. 9 of these with CK-MB release (median 2.3X ULN) Anatomic correlate of myonecrosis seen with contrast MRI (median 2.0 grams of myocardium)

10 0 10 20 30 40 50 60 70 80 90 100 CKMB (ng/ml) 151050 Hyper-enhancement mass of LV (g) Ricciardi Circulation 2001; 103:2780-2783 Correlation of post-PCI CKMB elevation and LV mass necrosis at contrast-enhanced MRI R=0.61P=0.02

11 CK-RELEASE dopo PCI Substrato fisiopatologico Correlati clinici, angiografici e procedurali Impatto prognostico Esiste un rapporto di causa/effetto?

12 Condizioni cliniche più frequentemente associate a rilascio enzimatico Età avanzata Pregresso infarto miocardico Pregresso intervento di bypass aorto- coronarico Ipercolesterolemia Insuccesso procedurale Insufficienza renale cronica Aterosclerosi sistemica

13 Clinical Characteristics associated with Post-Procedural CK-MB elevation (CK-MB <16U) 1675 Patients, Mount Sinay Hospital, NY, NY Kini A, JACC 1999;34:663-71 Elevated CK-MB (n=313) Normal CK-MB (n=1362) Female CCS class III-IV Renal failure Systemic Atherosclerosis Abciximab Use Betablocker therapy 3752716512730333103641 0.02 0.001 0.001<0.001<0.001<0.001<0.001 P value Charact(%) Age, hypertension,hypercholesterolemia, smoking, diabetes, prior MI, prior revascularization, LVEF, CHF, MVD, IABP were found not related to CK-MB elevation

14 Risk of troponin elevation after PCI a prospective substudy of SYMPHONY Positive TnI (n=230) Negative TnI (n=251) Age, y Female sex (%) Weight (kg) Current smoking (%) Diabetes (%) Family history of CAD (%) hypercholesterolemia (%) hypertension (%) 56 (48, 67) 21 86 (76, 99) 3815675547 59 (50, 66) 28 83 (74, 94) 3820555456 0.090.10.020.90.10.010.80.05 P value TnI >1.5 ng/ml ( Dimension, Dade Behring, Detection limit 0.05 ng/ml) Cantor WJ, submitted

15 Risk of troponin elevation after PCI a prospective substudy of SYMPHONY Positive TnI (n=230) Negative TnI (n=251) Chronic Angina Bypass Surgery Previous MI Previous PCI Stroke Heart Failure Chronic Renal Insufficiency 43161818250.452152318130 0.050.90.20.90.40.30.5 P value Medical history (%) TnI >1.5 ng/ml ( Dimension, Dade Behring, Detection limit 0.05 ng/ml) Cantor WJ, submitted

16 Risk of troponin elevation after PCI a prospective substudy of SYMPHONY Positive TnI (n=230) Negative TnI (n=251) Elective Recurr/Refract Ischemia Abrupt Closure Hemodynamic Instability (re)Infarction Days from qualyfying events 74141.7011 3 (2, 5) 77200.40.42 11 (5, 32) 0.50.050.10.30.001<0.001 P value Indication(%) TnI >1.5 ng/ml ( Dimension, Dade Behring, Detection limit 0.05 ng/ml) Cantor WJ, submitted

17 Plaque Characteristics associated with Post-Procedural CK-MB elevation (CK-MB <16U) 1675 Patients, Mount Sinai Hospital, NY, NY % 302520151050 AB1B2C P<0.001 N=207 N=223 N=880 N=365 Kini A, JACC 1999;34:663-71

18 Angiographic Characteristics associated with Post-Procedural CK-MB elevation (CK-MB <16U) 1675 Patients, Mount Sinai Hospital, NY, NY % 302520151050 Multivessel Intervention P<0.001 Single vessel Intervention P<0.001 Entire Group Diffuse CAD Focal CAD Kini A, JACC 1999;34:663-71

19 Risk of troponin elevation after PCI a prospective substudy of SYMPHONY Positive TnI (n=230) Negative TnI (n=251) Multivessel Intervention Target Vessel (native) Saphenous Vein Graft PTCAStent Atherectomy or Laser Abciximab Use Angiographic Success 107928852691163.6907741786 0.07N.S.0.10.50.0020.70.020.07 P value No difference Procedural Charact (%) TnI >1.5 ng/ml ( Dimension, Dade Behring, Detection limit 0.05 ng/ml) Cantor WJ, submitted

20 Device Characteristics associated with Post-Procedural CK-MB elevation (CK-MB <16U) 1675 Patients, Mount Sinay Hospital, NY, NY Kini A, JACC 1999;34:663-71 % 302520151050 PTCA*PRCA**StentPRCA+stent N=174 N=420 N=477 N=534 Otherdevices N=70 *PTCA vs non-balloon devices **PRCA vs Stent

21 Postprocedural cTnT elevation and total balloon inflation time Johansen O, Eur Heart J 1998;19:112-7 Prevalence(%) 50403020100 129631 Risk Ratio Total inflation time (sec) <180181-307>307 N= 75 patients

22 Cause di rilascio enzimatico Insuccesso procedurale Embolia coronarica Occlusione acuta transitoria Ampia dissezione Occlusione di collaterali Fenomeno no-reflow Ostruzione microvascolare 50-60%

23 CK elevations in Coronary Artery Interventions Angiographic correlates (Dobies R, AHA 1998) Prospective study: 774 pts Elevated CK (>160 mu/ml; MB>9.9 ng/ml) = 12% Angiographic evidence for CK elevation = 92% dissection thrombus side branch occlusion decreased final TIMI flow distal embolization abrupt closure 40% 24% 6% 17%7%

24 PCI, PLATELET AND MICROVASCULAR EMBOLIZATION Debries and platelet-thrombin-WBC micro-emboli

25

26 TIMI Myocardial Perfusion Grade and Maximum CK-MB 24 Hours Post-stent 0 0.5 1 1.5 2 2.5 TMPG 3TMPG 0/1/2 Maximum CK-MB / Upper Limit of Normal 2.23 + 2.70 p = 0.01 n = 24 n = 34 TIMI Grade 3 Flow: 100% CTFC: mean, 14.7 + 7.6 median, 13 TIMI Grade 3 Flow: 100% CTFC: mean, 19.2 + 7.5 median, 17.5, p=0.02 0.78 + 0.60 Gibson, AHJ, in press

27 Integrilin Improves Myocardial Perfusion After Stenting % With Normal Blush 69% 48% P=0.085 Placebo Integrilin 180/2/180 N=16N=27 % With Normal Blush DSA > 5.3 Gray 0 5 10 15 20 Circumference (cm) N=24N=32 Placebo Integrilin 180/2/180 11.7+ 6.9 15.0+ 7.7 P=0.079 Blush Circumference CM Gibson 2000

28 CK-RELEASE dopo PCI Substrato fisiopatologico Correlati clinici, angiografici e procedurali Impatto prognostico Esiste un rapporto di causa/effetto?

29 100 90 80 123456 TEMPO (anni) Sopravvissutil (%) p < 0.02 Controlli (n = 120) CK-MB >LSN (n = 253) Kong et al. JAMA. 1997 Clinical Relevance of CK elevation following PCI Northwestern University Experience 1984-1993

30

31 EPIC EPILOG EPISTENT Periprocedural CPK Elevation and Mortality in 3 RCTs of GP IIb/IIIa Inhibitors Topol, Circulation 2000;101:570.

32 Correlation Between Elevated Cardiac Markers and Long-term Mortality 1. Antman EM, et al. N Engl J Med. 1996; 335: 1342-1349. 2. Alexander JH et al. Circulation. 1999; Suppl 1:1-629. 5.7 % 9.2 % 12.6% 14.5% 19.9% 1-2 2-3 3-5 5-10 10 % mortality at 42 days <0.4<1.0 <2.0 <5.0 <9.0 9.0 2 4 6 8 0 % mortality at 6 months 2 1.7 % 3.4 % 3.7% 6.0% 7.5% 1.0 % 5 10 15 20 0 Cardiac Troponin 1 (ng/ML)CK-MB (x ULN)

33 Probability of Death by Max CK Ratio 0 0,05 0,1 0,15 0,2 0,25 02468101214161820 Max CK Ratio ST elevation Non ST elevation Probability of Death or MI by Max CK Ratio 0 0,05 0,1 0,15 0,2 0,25 05101520 Max CK Ratio NonST elevation ST elevation Probability of 6-month Events By Max CK Ratio across the spectrum of ACS: the GUSTO IIb study Savonitto S, JACC 2002, in press

34 01.02.0 Time (years) 0 40 20 60 80 100 Cumulative survival (%) Q-wave 3-5 x nl 1-3 x nl normal 5-8 x nl Impact on survival of Electrocardiographic Q-waves and enzimatic myocardial infarction Stone; Circulation 2001;104:642 > 8 x nl

35 CK-RELEASE dopo PCI Substrato fisiopatologico Correlati clinici, angiografici e procedurali Impatto prognostico Esiste un rapporto di causa/effetto?

36 CK- Release dopo PCI Causa di una prognosi peggiore.. … o marker di un rischio coronarico più grave?

37 Microinfarti e prognosi

38 CK-RELEASE AND CAUSES OF DEATH SUDDEN DEATH SUBSEQUENT REVASCULAR. MYOCARDIAL INFARCTION NO CARDIAC ORIGIN

39 CK-release e prognosi avversa: potenziali meccanismi Microinfarti = microrientri = suscettibilità a eventi aritmici Microembolizzazione: compromissione di circoli collaterali preformati = suscettibilità allischemia acuta e alle aritmie Microembolizzazione = alterata funzione del microcircolo

40 Coronary Microvascular Dysfunction in DCM Prognosis Neglia et al, Eur Heart J; 2000 (abs) PET MBF dip 1.36 ml/min/g

41 Epidemiology and prognostic impact of biochemical marker elevations after percutaneous coronary interventions A multicenter survey sponsored by the Italian Working Group on Atherosclerosis, Thrombosis and Vascular Biology and the ) Italian Society of Invasive Cardiology (GISE)Chairmen: Claudio Cavallini, MD, Ospedale S. Maria dei Battuti, Treviso Stefano Savonitto, MD, Ospedale Niguarda Ca Granda, Milan Roberto Violini, MD, Ospedale San Camillo, Rome

42 Primary objective Secondary objectives To evaluate prospectically the prognostic impact of CK-MB elevations >2x ULN after PCI on total mortality at 24 months To assess the incidence and risk determinantsTo assess the incidence and risk determinants of enzyme and marker elevations after PCI To assess the predictive value of each markerTo assess the predictive value of each marker of necrosis and inflammation, and their combination on the aggregate of death,MI and clinical restenosis To assess the risk of early (subacute stentTo assess the risk of early (subacute stent thrombosis) and late (clinical restenosis) events and their association with biochemical variables and predefined genetical polimorphisms

43 Inclusion criteria Exclusion criteria All of the patients undergoing PCIs during the study period Only patients not willing to participate in the study The study monitors will compare the study enrollment log with the Cath lab PCI log: centers enrolling <90% of their patients will be axcluded from the study PCI procedures and pharmacological interventions are to be carried out according to local routine

44 Blood sampling Baseline: immediately prior to PCI PCI 6 to 10 hours after the procedure 16 to 24 hours after the procedure Both plasmas and sera will be stored from each sampling, together with the cells for genetic determinations. All biological material will be sent to the central laboratory for biochemical and genetic determinations.

45 Biochemicalmarkers Mass CK-MB TnI C-reactive protein Serum Creatinine (substudy) Geneticdeterminations PlA 1 /PlA 2 polimorphism for the platelet GPIIIa receptor Polimorphism for the platelet GPIa receptor Polimorphism I/D for the ACE gene

46 TREVISO GENOVA MILANO Niguarda MERCOGLIANO BRESCIA (O.C.) CUNEO COTIGNOLA PAVIA UDINE NOVARA ROMA PARMA LEGNANO BOLZANO BRESCIA (P.A.) MIRANO ARRUOLAMENTO NEI VARI CENTRI

47 Month (yr 2000) 4039 patients Enrolment in the Italian PCI -BM (Biochemical Marker) study 16 participating centers Ist patient February 1 st Last patient October 31

48 Conclusioni Rilascio enzimatico dopo PCI o CABG: frequente Significato prognostico ?: sfavorevole(++ in > 5-10 volte LSN) Raccomandazione : prevenire Come trattare?: prevenzione secondaria The end


Download ppt "Stefano Savonitto, Claudio Cavallini Dipartimento di Cardiologia e Cardiochirurgia Angelo De Gasperis Ospedale Niguarda Ca Granda, Milano Divisione di."

Similar presentations


Ads by Google